(a) Field of the Invention
This disclosure relates to RNA aptamer specifically binding to a cancer metastasis-inducing domain of CEA (Carcinoembryonic antigen), a composition for prevention and/or inhibition and/or diagnosis of metastasis containing the RNA aptamer as an active ingredient, and a method of prevention and/or inhibition and/or diagnosis of metastasis using the RNA aptamer.
(b) Description of the Related Art
CEA (Carcinoembryonic antigen: CEACAM5, NCBI accession number: NP—004354), which is 180 KDa glycophosphatidylinositol (GPI)-anchored membrane glycoprotein, is heavily glycosylated. The CEA is consisted of N domain consisting of 107 amino acids at N-terminal, and 6 domains (A1, B1, A2, B2, A3, B3) repeated similarly to Ig (Immunoglobulin), each consisting of 178 amino acids, and the C-terminal is consisted of glycosylphosphatidylinositol membrane anchor. CEA has been studied as a cancer marker, and expressed in 70% of lung cancer and 50% of breast cancer, and colon cancer, stomach cancer and pancreatic cancer. Due to such characteristic, it is widely used clinically to diagnose cancer. CEA expression is known to be related to cell adhesion, inhibition of apoptosis and promotion of metastasis to liver. The level of CEA in blood is mainly used as a basis for determining prognosis after colon cancer surgery.
N domain of CEA is known to increase cell aggregation through the process of inducing interaction between CEA-positive (CEA-expressing) cells, thereby playing an important role to induce metastasis. In particular, 5 amino acids TELPK′ existing between N domain and A1 domain of CEA is known to be responsible for binding to kupffer cell that is associated with metastasis. It has been known that the TELPK′ is recognized by 80 kDa cell surface receptor on kupffer cell and greatly activate the next receptors by signal transduction, whereby CEA-expressing cells are brought into liver to induce metastasis.
In addition, since CEA is a Ca2+ independent intercellular adhesion molecule between homotypic cells, a possibility that a metastasis of CEA-expressing cells may occur by permeation through cell membrane to develop into cancer is suggested. As the result of analyzing CEA amino acid sequence of patients who have a large amount of CEA in blood stream but do not have metastasis to liver, among the patients with CEA-induced diseases, it is confirmed that PELPK region of CEA is mutated, This result suggests a possibility that mutation in PELPK may inhibit binding affinity of CEA to the receptor on the kupffer cell of liver, thereby inhibiting metastasis to liver, suggesting that a ligand to a cancer specific marker may be used as a strong means for cancer diagnosis and development of an effective anticancer therapeutic agent.